Electrode composition is of great importance in an electrochemical system, particularly in biochemistry, such as a biosensor. First, the electrode materials should be biocompatible with each other, and should not interfere with the standard behavior of any components in the system via reaction or catalysis. Second, the potential window of the electrode must be wide enough to perform the desired electrochemistry without degrading the electrode. Third, the electrode should resist undesired modification from the system, such as from proteins, salts, or other chemical species irreversibly binding to the surface and reducing the amount of active surface area. Fourth, some electrochemical assays require the chemical species to be tethered closely to the electrode. Fifth, in some applications, certain optical properties of the electrode (such as transparency or opacity to certain wavelengths) may be required. Finally, the target electrochemistry reaction should ideally proceed at a potential that excludes unproductive and/or unintended side reactions with components of the system.
Electron transfer kinetics also play an important part in an electrochemical system. Fast electron transfer kinetics are highly advantageous in electrochemistry because they allow for rapid equilibrium of the overall system following a redox event (Bard et al., Electrochemical Methods: Fundamentals and Applications, John Wiley & Sons, 96-115 (2001)). For voltammetric sensing platforms, electron transfer kinetics translate directly as the lag time of the sensor, and faster kinetics yield a sensor that rapidly reflects the surrounding electrochemical environment. For electrodes that actively drive redox processes, faster kinetics allow for less activation overpotential, allowing redox to occur near the standard potential (E0) of the target species. This can help reduce unwanted side reactions with other components of the system. In both cases, fast electron transfer kinetics help to make the electrochemical system respond predictably.
Electrode composition can affect electron transfer kinetics in an electrochemical system, and is of particular importance with respect to electrochemical species that do not undergo efficient electron transfer. In such systems, where additional processes are requisite for electron transfer (e.g., proton exchange, solvent reorganization, bond rearrangement, etc.) and substantially contribute to its rate, the Nernst equation does not apply effectively, and physical models built upon the Nernst equation are rendered inaccurate.
Quinones are an example of such electrochemical species that undergo inefficient electron transfer. Quinones are one of the most widely studied classes of electrochemically active molecules (see K. Thomas Finley, “Quinones,” Kirk-Othmer Encyclopedia of Chemical Technology, 1-35 (2005), which is incorporated herein by reference in its entirety. See also, Chambers, J. Q., “Electrochemistry of quinones,” Chemistry of Quinoid Compounds, 1:737-91 (1974); Chambers, J. Q., “Electrochemistry of quinones,” Chemistry of Quinoid Compounds, 2:719-57 (1988); Evans, D. H., Encyclopedia of Electrochemistry of the Elements, 12:1-259 (1978)). Quinones are a large class of organic redox molecules that find frequent use in a wide range of electrochemical systems, including biological, synthetic, industrial, medicinal, and fundamental academic applications, but often have inherently sluggish electron transfer rates to many electrodes.
Two broad factors contribute to these slow electron transfer rates for quinones. First, quinones undergo a two-proton, two-electron redox reaction. Thus, their voltammetric behavior is dictated by additional factors arising from proton transfer, including diffusion coefficients, temperature, pKa values for the relevant species, stability of the dianion, and possibly proton transfer rate constants (see Bae et al., “Enhanced electrochemical reactions of 1,4-benzoquinone at nanoporous electrodes,” Phys. Chem. Chem. Phys., 15:10645-53 (2013)). As a result, quinones do not conform to standard Nernstian behavior, necessitating large overpotentials at most electrodes to initiate redox, thus limiting their utility as potentiometric sensors. While structural changes to the quinone molecule can help to tune this inherent speed, such changes inevitably have other consequences on the molecular behavior as well (including shifted standard potential (E0), changes to solubility, etc.), and these additional consequences are often significant and cannot be generalized.
Second, quinones must be physically adjacent to the electrode before electron transfer can occur, as quinones undergo quasi-inner sphere electron transfer (Type M in the Robin-Day classification system) (see Rosokha et al., “Continuum of Outer- and Inner-Sphere Mechanisms for Organic Electron Transfer. Steric Modulation of the Precursor Complex in Paramagnetic (Ion-Radical) Self-Exchanges,” J. Am. Chem. Soc., 129(12):3683-97 (2007)). Thus, the electrode surface can introduce several additional factors that can reduce the observed electron transfer of the quinones from its optimal rate. For example, steric crowding at the electrode interface can have very significant effects (see DuVall et al., “Control of Catechol and Hydroquinone Electron-Transfer Kinetics on Native and Modified Glassy Carbon Electrodes,” Anal. Chem., 71(20):4594-4602 (1999)). Likewise, the electrostatic charge on the electrode surface can attract or repel quinones, and thereby exert a large influence on the electron transfer rate (see DuVall, et al., J. Am. Chem. Soc., 122(28):6759-64 (2000)). The diffusion rate of quinones and the variables that affect it (e.g., temperature, viscosity, etc.) can also impact electron transfer. Additionally, the overall surface area of the electrode is an important determinant in how much electron transfer is accomplished. For example, some electrodes, like indium tin oxide (ITO) electrodes, are further handicapped in that only a fraction of their surface area is actually electrochemically active. The vast majority of the physical interface of an ITO electrode is not conductive, as there are only small hot spots that are conductive and permit reactions to occur (see Marrikar et al., “Modification of Indium-Tin Oxide Electrodes with Thiophene Copolymer Thin Films: Optimizing Electron Transfer to Solution Probe Molecules,” Langmuir, 23(3):1530-42 (2007)). Thus, redox molecules, such as quinones, only react when in contact with one of the hot spots on the electrode, resulting in an even more inefficient electron transfer reaction.
Methods of improving electron transfer from an electrode to a target species are known. Electronic biochemical sensors can use an enzyme that oxidizes or reduces the target molecule, and then an electrode “regenerates” the enzyme by reducing or oxidizing it (respectively), and the total current passed by the electrode is used to quantify the amount of target molecule present. However, the enzyme is often a poor electron transfer partner with the electrode, so organic molecules are utilized as mediators, or shuttles, to help transfer the electron. U.S. Pat App. Pub. No. 2006/0113187 discloses that ruthenium, ferrocene, or ferricyanide derivatives can be employed in the solution to enhance electron transfer. U.S. Pat. Nos. 4,879,243 and 7,544,438 disclose that quinone derivatives can fulfill this function, but the electron transfer mediators/enhancers are dissolved into the analytical solution itself, and not localized onto the electrode. U.S. Pat. No. 7,384,749 discloses that the electron transfer enhancer/moiety (such as ferrocene) can be affixed to the target molecule for site-selective modification of nucleic acids. EP0187719 discloses utilizing a small molecule ((pyridinyl-methylene)hydrazinecarbothioamide (PHMC)) bound to the electrode surface to enhance electron transfer to species in solution without using an intermediary mediator. Organic layers can also be utilized in solar cell applications to enhance the conductivity between two electrode materials.